Castleman's Disease's Clinical Course and Management: A Study of 20 Cases

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5091-5091
Author(s):  
Jijun Liu ◽  
Lori C. Kim ◽  
Jianguo Tao ◽  
Lubomir Sokol
Keyword(s):  
Radiation Therapy ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Castleman’S Disease ◽  
Local Therapy ◽  
High Dose ◽  
Castleman's Disease ◽  
Off Label ◽  
Plasma Cell Dyscrasias

Abstract Abstract 5091 Background: Castleman's disease (CD), or angiofollicular lymph node hyperplasia, is a rare lymphoproliferative disorder that creates both diagnostic and therapeutic challenges. Three distinct histological variants including hyaline-vascular, plasmacytic and mixed were described. Clinically, patients can manifest with unicentric (UCD) or multicentric (MCD) Castleman's disease (Keller et al. Cancer 1972). Methods: Patients with a histologic diagnosis of CD from January 1999 to December 2009 at Moffitt Cancer Center and Tampa General Hospital were identified and their charts were reviewed. Relevant clinical, pathologic, laboratory data and treatment variables were recorded. Results: This case series consists of 20 consecutive patients including 11 unicentric cases and 9 multicentric cases. Median follow-up was 43 months. Unicentric CD (UCD): In the UCD group, 8/11 patients presented with mass and/or related compressive symptoms. The remaining 3 patients were asymptomatic. Only 2 patients had plasma cell (PC) histology, while the rest had hyaline vascular (HV) type. 2 patients had clonal B or plasma cell populations identified in the involved tissue. 4 (36%) patients had hypergammaglobulinemia. 9 (82%) patients received local therapy (surgery and/or radiation therapy) only. 4 patients achieved complete remission (CR) while 5 patients had recurrence after initial resection. Monoclonal antibodies including rituximab and CNTO 328, an anti-interleukin (IL)-6 monoclonal antibody were tested in 2 patients without response. Multicentric CD (MCD): In the MCD group, 67% patients had comorbidities including POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), Hepatitis C, acquired immunodeficiency syndrome (AIDS), and myelodysplastic syndromes (MDS). 4 patients had PC type and 5 had HV type. The majority of the patients (7/9) presented with constitutional symptoms, or hepatosplenomegaly or effusion/edema. Prognostic markers for plasma cell dyscrasia including beta-2 microglobulin, gammaglobulin or monoclonal protein were abnormal in 6 patients. Inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) or IL-6 were elevated in 3 patients. Local therapy as the main treatment modality resulted in CR in 2 patients. The 3rd patient achieved CR after autologous stem cell transplant (SCT). 2 patients died of the disease after 10 months and 56 months respectively. 3 patients were alive with disease and mild to moderate symptoms at the end of follow-up (36-44 months). All 4 patients that received high dose steroids had improvement of symptoms. 2 patients were treated with CNTO 328. One patient didn't tolerate secondary to infusional reaction while the other one had partial response (PR) and significant symptom improvement. Chlorambucil, melphalan and prednisone were used in one case following local therapy, leading to sustained CR. 2 patients were treated with high dose melphalan followed by autologous SCT. In the patient with POEMS, a CR was achieved while the patient with primary CD only had transient response. Rituximab was used alone or in combination with lenalidomide in 2 patients. The responses were either stable disease or short-lived PRs. Conclusion: We report here one of the largest recent retrospective cohort of patients with CD. The UCD is occasionally associated with hypergammaglobulinemia, monoclonal gammopathy (MGUS) and clonal plasma cells, mimicking clinical manifestation of plasma cell dyscrasias or lymphoplasmacytic lymphoma. Surgical resection is the primary curative treatment used for localized disease, although recurrences do frequently occur. Radiation therapy can be successfully used in patients with multiple relapses or in patients who are not surgical candidates. Systemic therapy has been attempted without much benefit. MCD is often associated with plasma cell dyscrasias and viral infections. Local therapy can be successfully used in selected cases. However, a majority (7) of cases with MCD will require systemic therapy including steroids or chemotherapy. Recently, anti–IL 6 monoclonal antibodies demonstrated efficacy in patients with MCD in phase I clinical study suggesting a role of IL-6 in pathophysiology of this disease. Disclosures: Off Label Use: There's no standard of care or FDA-approved drug for the treatment of Castleman's disease. All the agents discussed in this study including chlorambucil, melphalan, Rituximab, lenalidomide, CNTO 328(Siltuximab), bortezomib are considered off-label drug use.

scholarly journals Generalized Acquired Cutis Laxa Associated with Monoclonal Gammopathy of Dermatological Significance

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Sophia Z. Shalhout ◽  
Myrna R. Nahas ◽  
Reed E. Drews ◽  
David M. Miller
Keyword(s):  
Plasma Cell ◽  
Lupus Erythematosus ◽  
Monoclonal Gammopathy ◽  
Connective Tissue Disorder ◽  
Cutis Laxa ◽  
High Dose ◽  
Case Presentation ◽  
Plasma Cell Dyscrasias ◽  
One Year ◽  
Dose Prednisone

Background. Cutis laxa is a rare dermatosis that is inherited or acquired and clinically features loose, wrinkled, and redundant skin with decreased elasticity. This heterogeneous connective tissue disorder may be localized or generalized, with or without internal manifestations. Generalized cutis laxa often has a cephalocaudal progression and is attributed to inflammatory cutaneous eruptions, medications, and infections. Cutis laxa is also associated with several other conditions including rheumatoid arthritis, systemic lupus erythematosus, and plasma-cell dyscrasias. Case Presentation. We report an unusual case of a 35-year-old male with progression of generalized acquired cutis laxa and vasculitis that occurred over a period of one year. No cutaneous inflammatory eruption preceded or accompanied his decreased skin elasticity, and a biopsy of the skin showed elastolysis. His cutaneous manifestation led to systemic evaluation and an eventual diagnosis of smoldering multiple myeloma accompanied by aortitis and anemia. His myeloma and vasculitis were successfully treated with cyclophosphamide, bortezomib, and dexamethasone and high-dose prednisone, respectively, with no improvement to his cutis laxa. Conclusions. The presence of monoclonal gammopathy is strongly associated with several dermatological entities such as acquired cutis laxa. We propose a new term for the dermatological manifestations caused by paraproteinemia: monoclonal gammopathy of dermatological significance, or MGODS, and stress the evaluation of an underlying gammopathy in the setting of certain dermatologic conditions, including scleromyxedema and amyloidosis. We present a case of a newly acquired cutis laxa secondary to plasma-cell dyscrasias that exemplifies MGODS, alongside a brief literature review, and underscore the clinical relevance of monoclonal gammopathies of dermatological significance.

Castleman's disease in the orbit. A 20-year follow-up

2002 ◽  
Vol 80 (5) ◽  
pp. 540-542 ◽  
Author(s):  
Ghassan Ayish Alyahya ◽  
Jan Ulrik Prause ◽  
Steffen Heegaard
Keyword(s):  
Castleman’S Disease ◽  
Castleman's Disease

scholarly journals A Prospective Study and Identification of Genomewide Association Markers of Familial Predisposition to Plasma Cell Dyscrasias

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 8-8
Author(s):  
Adam S Sperling ◽  
Rebecca Georgakopoulou ◽  
Mehmet Kemal Samur ◽  
Christine Ivy Liacos ◽  
Brittany E Sandoval ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
B Cell ◽  
Board Of Directors ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Research Funding ◽  
Advisory Committees ◽  
Familial Predisposition ◽  
Plasma Cell Dyscrasias ◽  
Second Degree

Introduction: An increased inherited risk for the development of plasma cell dyscrasias (PCDs) has long been suspected, however to date, only a limited number of potential genomic risk loci have been described. To characterize the inherited risk and facilitate identification of additional risk loci it is important to combine detailed pedigrees with extensive genetic analysis. To identify familial PCDs we initiated a prospective study with active recruitment of a large cohort of patients with PCDs and active screening of their relatives combined with tissue banking and subsequent genetic analysis. Methods: All patients in the Department of Clinical Therapeutics diagnosed with PCDs between January 2017 and January 2019, were offered enrollment in the study. Following informed consent, 1st and 2nd degree relatives over the age of 30 were eligible for screening. A detailed family pedigree was created for each index case with special focus on family history of PCDs, B-cell lymphomas, or other hematologic or solid malignancies. As a control, subjects' spouses were also screened. Screening included serum protein electrophoresis with immunofixation. In families where an additional member was identified with a PCD or B-cell malignancy, peripheral blood was collected from consenting family members over the age of 18 for further genetic analysis. Samples from affected individuals were profiled using whole genome sequencing (WGS) and unaffected individuals were genotyped using Axiom Arrays. Data were analyzed using Axion Array Suite and plink and GATK toolkit with BWA. Results: Of 1,084 patients screened for participation in the study; 752 had multiple myeloma (MM), 77 had smoldering MM, 81 a monoclonal gammopathy of undetermined significance, 93 Waldenström's Macroglobulinemia and 81 had AL amyloidosis. 176 (16.2%) patients refused to participate in the study, while 44 (4.1%) patients were ineligible for further screening due to the absence of a living first- or second-degree relative. The median number of screened first or second-degree relatives per index patient was 3 (range 1 to 10). The median age of index cases was 65 years, offspring was 37 years, second-degree relatives was 65 years, and spouses was 65 years. The incidence of a PCD among second-degree relatives was 4.5%, while it was 0.6% among offspring. As a control group, the incidence of PCDs among spouses was 2.6%. Overall at least one additional member (beyond the index patient) with a monoclonal gammopathy was detected in 98 families (11.3%). In 57 families (6.6%) there was a positive history of at least one additional first- or second-degree relative with a PCD or B-cell malignancy. In addition, 41 new cases of monoclonal gammopathy (4.7%) were identified through the screening process associated with this study. To identify genetic loci that could be associated with a predisposition to development of PCDs, genetic analysis was performed on the most heavily affected 18 families, those with at least three affected members or with early onset disease (i.e. PCD diagnosed before age 50). We have evaluated 838,750 SNPs from 103 samples from 18 families. 30 samples were from affected members and 73 from unaffected members. We found eight SNPs (rs13233413, rs11648113, rs59444635, rs148480125, rs113556240, rs11547122, rs671880, rs4726610) that are significantly enriched in affected members with a p-value below the suggestive cut-off of <1e-5. The top candidate was in the untranslated region (UTR) of TSPAN33, a marker of activated and malignant B-cells. We did not detect any significant enrichment in germline mutations in previously reported genes associated with familial PCD risk such as KDM1a, KRAS or DIS3. Functional annotation of the 8 SNPs identified here showed that rs148480125, located in the promoter region of the apoptosis regulator SIVA1, is predicted to impact the allele specific expression level. Further validation work is ongoing. Conclusions: Our active prospective screening approach to identify familial predisposition to PCDs revealed that 11.3% of patients had families with at least one additional affected member and some families had a substantially higher incidence of PCDs with earlier onset. Study of these high-risk families have identified genomewide association markers which in future may help us define familial predisposition to plasma cell dyscrasias. Disclosures Gavriatopoulou: Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Terpos:Amgen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Other: travel expenses , Research Funding; Celgene: Honoraria; Sanofi: Honoraria; BMS: Honoraria. Kastritis:Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria. Munshi:Janssen: Consultancy; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy; Legend: Consultancy; Amgen: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; C4: Current equity holder in private company; Adaptive: Consultancy. Dimopoulos:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau.

Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up

Lung Cancer ◽  
2014 ◽  
Vol 83 (1) ◽  
pp. 78-82 ◽  
Author(s):  
Emilio Minatel ◽  
Marco Trovo ◽  
Jerry Polesel ◽  
Tania Baresic ◽  
Alessandra Bearz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Malignant Pleural Mesothelioma ◽  
High Dose ◽  
Pleural Mesothelioma ◽  
Long Term Follow Up

scholarly journals A Case of Spondyloarthritis in Patient Affected by Unicentric Castleman’s Disease Effectively Managed with Surgery Resection and Tocilizumab Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
M. Filippini ◽  
S. Cartella ◽  
O. Bonzanini ◽  
E. Morello ◽  
A. Tincani
Keyword(s):  
Marked Improvement ◽  
Late Onset ◽  
Castleman’S Disease ◽  
Castleman's Disease ◽  
Hla B27 ◽  
History Of ◽  
Inflammatory Drugs ◽  
Rheumatologic Manifestations ◽  
Surgery Resection

A 38-year-old woman was referred to our hospital for rheumatologic manifestations (migrant arthritis and tenosynovitis), without psoriasis or family history of psoriasis, gastroenteric manifestations, or recent genitourinary infections. The instrumental and laboratory tests have suggested a diagnosis of undifferentiated seronegative HLA-B27-positive spondyloarthritis with predominantly peripheral involvement. The symptoms were very severe and resistant to anti-inflammatory drugs and steroids. She had a history of hyaline-vascular unicentric Castleman’s disease (HBV, HIV, and HHV-8 negative) treated with surgery resection. After a first pharmacological attempt with sulfasalazine (suspended for urticarial rash), we managed the patient with monotherapy tocilizumab 8 mg/kg, with full response of rheumatologic manifestations. The efficacy of tocilizumab was confirmed even after a follow-up of three years. Our experience seems to describe a new late-onset autoimmune disease (only 21 cases described in literature) potentially related to Castleman’s disease. The patient experienced marked improvement from IL-6-based therapy (tocilizumab).

A Pilot Clinical Trial of Surgical Adjuvant Treatment with High-Dose 6S-Leucovorin/5-Fluorouracil and Radiation Therapy for High-Risk Rectal Carcinoma

1994 ◽  
Vol 80 (5) ◽  
pp. 335-338 ◽  
Author(s):  
Stefano Cascinu ◽  
Antonio Veraldi ◽  
Gian Paolo Foglietti ◽  
Roberto Ghiselli ◽  
Vittorio Saba ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Rectal Carcinoma ◽  
Adjuvant Treatment ◽  
Randomized Trials ◽  
Dose Intensity ◽  
High Dose ◽  
Radiotherapy Alone ◽  
The Mean

Aims and background The study was performed to evaluate the feasibility of combining leucovorin (LV) with 5-fluorouracil (5FU) and radiation therapy as adjuvant treatment for high-risk rectal carcinoma. Methods Twenty-five patients with histologically proven adenocarcinoma of the rectum, at high-risk of recurrence after potentially curative resection (T3 NO, T any N1-2; MO), received 5FU (370 mg/m2) and 6S-LV (100 mg/m2) on days 1-5, 4 and 8 weeks after surgery. On treatment day 64, radiotherapy on the pelvis (50 Gy) was initiated. Finally, three further courses of 5FU/LV were given at intervals of 4 weeks beginning 28 days after the completion of radiotherapy. Results The treatment was generally well tolerated. We observed only 2 cases of grade III toxicity (diarrhea) during the third cycle of chemotherapy. No severe complications were recorded following the use of radiotherapy. The mean overall 5FU dose intensity was 92%. After a median follow-up of 24 months, 4 patients had relapsed (liver, lung, and pelvis, 2 cases). Conclusions The association of LV to 5FU and radiation therapy seems to be feasible, with acceptable toxicity. The advantage of this combination, in terms of recurrence rate and survival with respect to 5FU/radiotherapy alone, will have to be evaluated in randomized trials.

scholarly journals Differential diagnosis of monoclonal gammopathy of undetermined significance

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 595-603 ◽  
Author(s):  
Giampaolo Merlini ◽  
Giovanni Palladini
Keyword(s):  
Differential Diagnosis ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Cell Clone ◽  
Organ Damage ◽  
Organ Injury ◽  
Al Amyloidosis ◽  
Monoclonal Protein ◽  
Undetermined Significance

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder occurring in 4.2% of adults > 50 years of age, which can progress into symptomatic diseases either through proliferation of the plasma cell clone, giving rise to multiple myeloma and other lymphoplasmacellular neoplasms, or through organ damage caused by the monoclonal protein, as seen in light-chain amyloidosis and related conditions. Differential diagnosis of asymptomatic and symptomatic monoclonal gammopathies is the determinant for starting therapy. The criteria for determining end-organ damage should include markers of organ injury caused by the monoclonal protein. Patient assessment and optimal follow-up are now performed using risk stratification models that should also take into account the risk of developing AL amyloidosis. Patients with low-risk MGUS (approximately 40% of all MGUS patients) need limited assessment and very infrequent follow-up. The ongoing development of novel molecular biomarkers and advanced imaging techniques will improve the identification of high-risk patients who may benefit from early therapeutic intervention through innovative clinical trials.

Plasmapheresis as a Therapeutic Option for Castleman’s Disease [CD].

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4761-4761
Author(s):  
Maged Khalil ◽  
Shetra Sivamurthy
Keyword(s):  
Ct Scan ◽  
Single Agent ◽  
Castleman’S Disease ◽  
Immune Dysregulation ◽  
High Dose ◽  
Medical Illness ◽  
Axillary Lymph ◽  
Castleman's Disease ◽  
Peripheral Smear ◽  
Normal Urine

Castleman’s Disease (CD) is a distinct pathologic entity with clinical heterogeneity. with hyperimmune or immune dysregulation, There is no known standard treatment. A variety of therapies have been tried including Surgery, Radiation, steroids, single agent chemotherapy, multi agent chemotherapy, Rituximab and monoclonal antibody to IL-6. Plasmaphersis which was successful in this patient has not been tried before in CD. Case report 31 year old female with no significant past medical illness admitted with 10 days history of fever, abdominal pains. CT scan of chest and abdomen showed small mediastinal and left axillary lymphadenopathy. Physical examination revealed a palpable 2 cm rubbery mobile non tender left axillary node and mild tenderness over right upper quadrant, otherwise unremarkable Laboratory examination on admission showed BUN 17 mg/dL, Creatinine 1.4 mg/dL, Potassium 5.5 meq/L, Calcium 8.4 mg/dL, Total Protein 6.6 g/dL, Albumin 2.9 g/dL, Bilirubin 1 mg/dL, Alkaline phosphatase 427 U/L, AST 27 U/L, ALT 26 U/L, GGT 288 U/L. WBCs 12,400, with 70% Neutrophils, 7%Bands, 10%Lymphocytes, 11% Monocytes and 2%. Eosinophils, HGB 12 g/dL, Platelets 630,000. Peripheral smear was normal. ESR 65 mm/hr. ANA-negative. Serum Complement C4 22 mg/dL and C3 116 mg/dL. Monospot test- negative. Toxo titer was negative. PT 15.5” and PTT 38”. Serum Protein Electrophoresis and seum immunofixation were normal. Urine Bence Jones Protein was negative. Serum Cryoglobulin was negative. Urinalysis was normal. Hepatitis profile was negative. Hepatobiliary scan was normal. Hospital Course- She continued to have fever despite negative cultures. Renal functions worsened over the first few days of admission, BUN and Creatinine increased to 27 mg and 2.3 mg respectively. Left axillary lymph node biopsy showed Hyaline vascular Castleman’s disease like changes. Biopsy of right kidney was done showed Chronic Thrombotic microangiopathy with predominant glomeruler involvement. Bone marrow biopsy and Immunohistochemistry of the aspiration were normal. HHV- 8 antibody was negative. HIV screening was also negative. She was started on Prednisone 1mg/kg/day without clinical or laboratory improvement. BUN increased to 101mg/dL and Creatinine to 3.8mg/dL with generalized anasarca and reduced urine out put. Hgb dropped to 6.7gms/dl, Platelets 27,000 and WBCs 18,700 with neutrophilia. Peripheral smear showed no schistocytes at any time. Since her condition was worsening despite high dose of steroids, patient was started on daily Plasmaphersis with noticeable daily clinical and laboratory improvement. After 26 sessions of Plasmapheresis all the hematological and renal abnormalities improved with clearance of anasarca and normal urine out put. At the time of discharge - CBC showed WBCs 13,000, Hgb 11.1 g/dL, Platelets 123,000. BUN 25mg/dL and Creatinine 0.5 mg/dL. The repeat CT scan revealed no lymphadenopathy. Two year later she remains in complete remission with normal renal function and normal blood counts. Conclusion Plasmaphersis can help in controlling the Hyper immune or immune dysregulation, consequences of Castleman’s disease and may be an option in treating severe systemic manifestations of CD.

Clinical, Biochemical, and Radiographic Responses to Rituximab Combined with Liposomal Doxorubicin (R-Dox) in HIV-Infected Patients with Severe Kaposi Sarcoma-Associated Herpes Virus (KSHV) – Associated Multicentric Castleman's Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1651-1651
Author(s):  
Thomas Uldrick ◽  
Mark N. Polizzotto ◽  
Deirdre O'Mahony ◽  
Karen Aleman ◽  
Kathy Wyvill ◽  
...  
Keyword(s):  
Liposomal Doxorubicin ◽  
Castleman’S Disease ◽  
Biochemical Response ◽  
Additional Patient ◽  
Castleman's Disease ◽  
Multicentric Castleman’S Disease ◽  
Radiographic Response ◽  
Additional Therapy ◽  
Multicentric Castleman's Disease

Abstract Abstract 1651 Poster Board I-677 Background KSHV-associated multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder characterized by fever, splenomegaly, adenopathy, hypoalbuminemia, hyponatremia, cytopenias, elevated inflammatory markers, and a waxing and waning course. Most MCD arising in HIV-infected patients is KSHV-associated. Historically, prognosis has been poor. There is no standard therapy, although benefit has been reported with cytotoxic chemotherapy, interferon-á, retinoic acid and ganciclovir. Rituximab has reported activity in KSHV-MCD, but may not be sufficient as monotherapy in patients with severe disease, and can be associated with worsening of Kaposi's sarcoma (KS). Within a natural history study of KSHV-MCD, we evaluated the treatment effects of R-Dox on correlates of disease activity in patients with severe MCD or MCD with concurrent KS. Methods Patients with biopsy confirmed MCD that was severe or accompanied by severe KS were treated with liposomal doxorubicin 20mg/m2 plus rituximab 375 mg/m2 every 21 days until substantial clinical improvement or disease progression. Post R-Dox therapy, discussed below, was used to consolidate or maintain responses. Clinical, biochemical and radiographic response were evaluated individually using protocol-defined criteria. Overall complete responses (CR) required normalization of all clinical, laboratory or radiographic abnormalities attributed to MCD lasting at least 3 weeks. Results Twelve patients (1 woman, 11 men) have been treated with R-Dox to date. Patient characteristics: median (med) age 43 (range 34-55); all were on HAART, med CD4 331 cells/μL (21-1598), HIV viral load <50 copies/mL in 10 patients. Med number of prior therapies 2 (0-8); concurrent KS (5); dependent on steroids (3); patients hospitalized during first cycle (6). Med baseline values for biochemical response parameters: C-reactive protein 9.7 mg/dL (0.4-21.0), albumin 2.7 mg/dL (1.5-3.4), sodium 133 mEq/L (126-140), platelets 70 K/uL (10-377), hemoglobin 9.4 g/dL (6.8-12.0). 11 had diffuse adenopathy and all had splenomegaly, med spleen 18.5 cm (12.5-28 cm). Patients received med 4 cycles (3-9) of R-Dox. All patients met criteria for clinical CR after a med 2 cycles (range 1-5). Best biochemical response was CR in 9 (75%) and partial response (PR) in 1 (8%); 2 (17%) had stable biochemical parameters. Best radiographic response was CR in 6 (50%) and PR in 6 (50%) with a med 5 cm (+0.5 cm, -10 cm) decrease in spleen size. Best biochemical response was achieved after med 3 cycles (1-7), and best radiographic response after med 3 cycles (2-5). 2 of 12 had an overall CR at completion of R-Dox. Post R-Dox therapy included: IFNá (8), high-dose AZT + valganciclovir (2), additional liposomal doxorubicin (1). To date, another 6 patients achieved overall CR with additional therapy. Concurrent KS improved in 4 of the 5 patients affected. With a median potential follow-up of 25.5 months (actual follow-up range from 5.5+ to 41+ months), 9 of 12 patients have had no MCD relapse after starting R-Dox, 2 patients had recurrent MCD flares (months 7 and 17) that responded to additional therapy and 1 patient had progressive MCD during cycle 6 associated with worsening KS, and died at month 6 of central pontine myelinolysis. He was found to have primary effusion lymphoma at autopsy. An additional patient died of pneumonia (month 17). Toxicity was minimal. 9 patients had infusion reactions (Gr. 1 = 3, Gr. 2 = 4, Gr. 3 = 2) with the first dose of rituximab. 9/55 cycles were complicated by neutropenia (Gr. 2 = 7, Gr. 3-4 = 2). There were no infectious complications. Conclusions R-dox is highly effective in heavily pretreated patients with severe KSHV-MCD or MCD with concurrent severe KS. Further evaluation of R-Dox in patients with severe KSHV-MCD is ongoing. Disclosures Off Label Use: Rituximab and Liposomal Doxorubicin are being explored in the treatment KSHV-MCD.

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